The purpose of this proposal is to develop a validated physiological model of the human physiology, especially the cardio-renal axis, for submission to the FDA Medical Device Development Tool pilot program. The model will be used to aid in the development and regulation of medical devices designed to treat hypertension. Examples include devices for renal nerve ablation, electrical stimulation of the carotid baroreceptors and creation of an A-V Fistula. Given that 12-15% of US patients with resistant hypertension on 4 or more drugs, at a price tag of $11-$17 billion, the importance of a tool that streamlines the time for design, testing, and regulation of a non-pharmacological device is clear. The multifactorial nature of hypertension complicates its treatment, and no device intervention is guaranteed to successfully treat each patient. Our physiological model is a powerful tool for understanding the impact of interpatient variability on antihypertensive therapies and confirming the correctness of using a specific device for blood pressure control. In Phase II, we will demonstrate a validated and documented model, extending HumMod, our existing model of human physiology, to include more intracellular signaling and adaptation, as well as a multilevel, detailed circulation. The aims of this study include: 1) the complete transfer of the model from a proprietary simulation environment into Modelica, a multi- domain language for modeling of complex systems, 2) documentation of model evidence and structure in a searchable repository, and 3) a verification suite to ensure that the model functions correctly.